While sporadic data is available regarding the impact of risk factors on the development and behavior of intracranial aneurysms (UIAs), an understanding of how potential risk factors interact remains largely unknown. A better understanding of risk factors may allow for more precise risk assessment when counseling patients with UIAs. While hypertension and smoking are universally accepted independent risk factors for UIA development, the effects of other medical and lifestyle risk factors, such as hypercholesterolemia and alcohol consumption, are less clear. Furthermore, the combined impact of well-established risk factors remains to be established. To further probe this issue, Vlaket et al conducted a study to evaluate independent risk factors and the joint effect of risk factors for UIAs.1 The significance of improving the current state of knowledge of these risk factors cannot be understated, particularly when considering that roughly 3% of the general population harbors an UIA and the potentially devastating outcome of aneurysmal subarachnoid hemorrhage (aSAH).2,3 The results of the study are published in the February 2013 issue of Stroke.1
Between September 2006 and September 2009, the authors enrolled 206 UIA patients at their institution in the Netherlands. The inclusion criteria for the study group were: 1) patients harboring a UIA confirmed by either computed tomography angiography, magnetic resonance angiography, or standard angiography, 2) patients with a negative history of aSAH, 3) patients 18 years or older, and 4) patients who speak Dutch. For comparison to the study group, the authors recruited 574 control patients between January 2009 and January 2010 from within the catchment area of their institution. All subjects completed a questionnaire that collected data on demographics, height, weight, smoking, alcohol consumption, physical activity, medical history, and family history of stroke. The patients were specifically asked about previous diagnosis of diabetes mellitus, heart disease, hypertension, hypercholesterolemia, or migraine. Additionally, for UIA patients, the authors obtained indication for imaging data.
Multivariate statistical analysis demonstrated that current smoking status, hypertension, and family history of stroke independently increased the risk for UIA (odds ratios of 3.0, 2.9, and 1.6, respectively). On the other hand, hypercholesterolemia and habitual physical exercise independently decreased risk of UIA formation (odds ratios of 0.5 and 0.6, respectively). The odds ratios of the other studied risk factors are summarized in the Table.1 In accordance with previous data, hypertension and current smoking were the strongest independent risk factors for UIA.2,4,5 However, the authors found that the joint risk of smoking and hypertension was higher than the sum of the individual risks (odds ratio of 8.3 compared to 3.0 for smoking alone and 2.9 for hypertension alone).
Despite the inherent limitations of the study design, the findings of this study are interesting and merit further attention both for individual patients and populations. For instance, the finding that hypercholesterolemia decreased risk of UIA conflicts with the conclusions of previously published reports.6,7 Furthermore, the novel observation that the joint risk of smoking and hypertension is greater than the sum of the individual risks warrants further investigation. This issue may emerge as critical to families who are at high risk for UIA.8 The observation that regular physical exercise was associated with decreased presence of UIAs is thought-provoking and should be examined in larger studies. Studies such as this will likely bring us closer to a more comprehensive understanding of UIA risk factors. Ultimately, advanced computing will be needed to incorporate risk factors related to lifestyle, genetics, hemodynamics, aneurysm wall biology, and other unknown factors into comprehensive equations that allow physicians to individualize risk assessments and perhaps pave the way for rational screening strategies. This will bring us closer to individualized healthcare for patients with UIAs.
1. Vlak MH, Rinkel GJ, Greebe P, Algra A. Independent risk factors for intracranial aneurysms and their joint effect: a case-control study. Stroke. 2013;44(4):984–987.
2. Vlak MH, Algra A, Brandenburg R, Rinkel GJ. Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. Lancet Neurol. 2011;10(7):626–636.
3. de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ. Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry. 2007;78(12):1365–1372.
4. Chien A, Liang F, Sayre J, Salamon N, Villablanca P, Vinuela F. Enlargement of small, asymptomatic, unruptured intracranial aneurysms in patients with no history of subarachnoid hemorrhage: the different factors related to the growth of single and multiple aneurysms [published online ahead of print]. J Neurosurg. 2013.
5. Juvela S, Poussa K, Porras M. Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke. 2001;32(2):485–491.
6. Gu YX, Chen XC, Song DL, Leng B, Zhao F. Risk factors for intracranial aneurysm in a Chinese ethnic population. Chin Med J (Engl). 2006;119(16):1359–1364.
7. Inagawa T. Risk factors for the formation and rupture of intracranial saccular aneurysms in Shimane, Japan. World Neurosurg. 2010;73(3):155–164; discussion e123.
8. Broderick JP, Brown RD Jr, Sauerbeck L, et al.. Greater rupture risk for familial as compared to sporadic unruptured intracranial aneurysms. Stroke. 2009;40(6):1952–1957.